1. Field of the Invention
The present invention relates generally to the field of molecular biology, bile duct disease, and diagnosis. More particularly, it concerns methods for treatment of a subject by administration of a melatonin signaling modulator. The invention also generally pertains to methods for diagnosis of biliary tract disease, such as cholangiocarcinoma.
2. Description of Related Art
Diseases of the biliary tract are a common cause of morbidity and mortality in the U.S. Cancer of the biliary mucosa, cholangiocarcinoma (CCA), results from the malignant transformation of cholangiocytes, which line intrahepatic and extrahepatic bile ducts of the liver (Lazaridis and Gores, 2005). The pathogenesis of CCA is linked to chronic biliary proliferation and inflammation, which occurs in cholestatic liver diseases including primary sclerosing cholangitis (PSC). CCA is clinically silent and mostly diagnosed as an advanced disease resulting in limited therapeutic options (Malhi and Gores, 2006). Recent evidence indicates that the proliferating biliary mucosa serves as a neuroendocrine compartment during the pathogenesis of liver diseases, and as such, secrete and respond to hormones, neurotransmitters and neuropeptides contributing to the autocrine and paracrine pathways that positively and/or negatively modulate liver inflammation, fibrosis and biliary carcinogenesis (Alvaro et al., 2007). While advances have been in the understanding of the neuroendocrine factors that modulate biliary mucosa growth during the progression of liver diseases and the ultimate development of CCA, unfortunately, viable therapies for the management of CCA remain elusive. On the other hand, currently cholangiocarcinoma diagnosis relies on examination of tumor tissue, which may be inconvenient for early detection.
There remains, therefore, a need of novel methods for diagnosis and therapy of diseases of the biliary tract, such as cholangiocarcinoma.